The mission of the Mouse Mutant Resource (MMR) at The Jackson Laboratory (TJL) is to provide mouse models for biomedical and biological research. Spontaneous mutations continue to be a major source of mouse models for human disorders. They complement specifically targeted mutations and have the advantage that they are first recognized by relevant phenotypes and do not require prior knowledge of the underlying genes. The specific objectives of the MMR program in this renewal are to (1) characterize new mouse mutants genetically, phenotypically, and pathologically;(2) establish the new mutations in strains suitable for further analysis;(3) preserve the mutations as frozen embryos or gametes to assure their continued availability and as DNA for future molecular analysis;(4) provide mutant mice and controls to other investigators, and (5) provide information about the mutant mice to the scientific community. The new mutations are discovered as phenotypic deviants appearing in The Jackson Laboratory's large breeding colonies. They are characterized genetically by determining their modes of inheritance, testing them for allelism with known mutations that produce similar phenotypes, and determining their chromosomal locations. Each new mutant is characterized phenotypically by observing its growth, viability, fertility, life span, and behavior and by defining its anatomical, histopathological, and physiological abnormalities. For those mutants with phenotypes that resemble important human diseases, further genetic and molecular analyses are undertaken to identify the underlying genes. The MMR team has expertise in hearing, vision, bone biology, reproduction, and neuropathology and collaborates with experienced investigators in other fields. All new mutants are published in peer-reviewed journals or presented on the MMR and TJL web sites, and related information is made available-through the Mouse Genome Database. Relevance of project to human health: The research in this project will provide new mouse models for specific human disorders and for basic biomedical research to understand biological systems affected by human diseases. Mouse models enable scientists to understand the causes and pathologies of similar human diseases so that prevention strategies or therapeutics for these diseases can be developed. In addition, therapies or drugs can be tested on mouse models prior to human trials to assess efficacy and safety.